Chemistry for Sustainable Development 11 (2003) 557–565
557
Halogenated Phenol Compounds in Lichens and Fungi
VALERY M. DEMBITSKY1 a nd GENRICH A. TOLSTIKOV2
1
Department of Pharmaceutical Chemistry and Natural Products, School of Pharmacy,
The Hebrew University of Jerusalem, P. O. Box 12065, Jerusalem 91120 (Israel)
E-mail: dvalery@cc.huji.ac.il
2
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy
of Sciences, Pr. Akademika Lavrentyeva 9, Novosibirsk 630090 (Russia)
E-mail: gtolstik@nioch.nsc.ru
(Received February 14, 2002)
Abstract
The structures of hundred halogenated metabolites of phenolic nature generated by lichens and fungi are
considered. The groups of depsides, depsidones, fungoid metabolites are marked out. The problems related to
biological activity are discussed.
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Lichen depsides and depsidones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Fungi phenol metabolites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
INTRODUCTION
The amount and structural variety of compounds containing phenolic structural unit is
innumerable in n ature. Examples of the isolation and identification of the halogen ated phenolic compounds of complicated structure become more and more numerous. As one would
expect, substances with extremely valuable
biological activity are discovered among halogen-containing compounds of phenolic type. A
very indicative example is the recent discovery of strobilurine compounds, fungoid metabolites which served as a basis fort he design of
a new class of fungicides to be introduced into
the agriculture [1, 2]. Many fungi synthesize
chlorin ated phenols, which are likely to cause
various diseases in plants, leading to plant death.
Lichens are symbiotic organisms composed of
557
–
561
a photobiont, which is a microalga or a cyanobacteria, on the one hand, and a mycobiont,
which is a fungus of Ascomycetes, on the other
hand [3]. Lichens generate a number of biologically active molecules, among which a noticeable role is played by halogen ated phenol compounds.
In the review, we consider typical lichen
metabolites, such as depsides and depsidones,
as well as complicated phenolic metabolites of
fungi.
LICHEN DEPSIDES AND DEPSIDONES
Depsides are esters formed by the derivatives of p-oxybenzoic acid and phenols. They
comprise a small group of polyketides and are
generated mainly by lichens. For example, the
558
VALERY M. DEMBITSKY a nd GENRICH A. TOLSTIKOV
most widespread chlorine-containing depside
chloroatranorin (1) was discovered in more than
40 lichen species: Evernia prunastri [4–6],
Pseudevernia furfuracea [7, 8], P. intensa [9],
Parmelia perlata [10, 11], P. pseudoreticulata
[11], P. olivetorum [12], P. cryptochlorophaea
[13], P. tinctorum [9–14], P. pseudofatiscens [15],
P. horrescens [15], P. damaziana [16], P. furfuracea [17], Buellia canescens [18, 19], Ramalina siliquosa [20], R. druidarum [9], Lecidea carpathica [21], Lecidea sp. [22], Phiscia picta [23],
Cetralia cetrarioides [9], C. japonica [9], Usnea
canariensis [9], Hypogymnia physodes [9], H. billardieri [24], H. enteromorpha [24], H. lugubris
[24], H. subphysodes [9], Anaptychia neoleucomelaena [9–25], Menegazzia asahinae [26], M. terebrata [26], M. dispora [27], Platismatia glauca [28], Parmotreama demethylmicrophyllinicum [29], P. praesorediosum [30], Lacanora braccha [31], L. epibryon [31], L. rupicola [9, 32]
and L. gangaleoides [9, 33].
Tumidulin (2), a less widely spread lichen
metabolite, was discovered only in Ramalina
genus: R. ceruchis, R. flaccescens, R. tumidula,
R. inanis, R. cactacearuum, R. peruviana and
R. chilensis [9, 25, 33–36]. The Erioderma
wrightii lichen generates wrightin (3) [37], (4)–
(10) metabolites were detected in Erioderma
sp., and depside (11) was isolated from extracts of Pseudocyphellarie pickeringii [40]. Me-
tabolite (12) was isolated from the extracts of
Lecanora sulphurella lichen; its structure was
confirmed by synthesis [41].
3-Chlorodivaricatinic acid (13), 3-chlorostenosporic (14) and 3-chloroperlatolic (15) acids
were discovered in Thelomma mammosum [42]
and Dimelaena sp. lichens [43]. Guisinol (16)
was discovered in isolates from marine fungus
Emericella unguis (known also as Aspergillus
unguis) [44]. This is the first and sole representative of depsides detected not in lichens;
it exhibits high antibacterial activity [44].
Depsidones are the derivatives of di phenyloxide containing the heterocyclic system of
1,4-dioxacycloheptanone-7 as a result of the
formation of itramolecular ester bond. The first
representative of depsidones, n amely, di ploicin (17), was isolated in 1904 by Zopf from a
lichen of undetermined species [45]. Subsequent
research showed that (17) is present in Buellia
canescens [18, 19, 46, 47] and Lecidea cargaleoides [21] lichens.
Though gangaleoidin (18) was discovered
more than 65 years ago in Lecanora gangaleoides lichen [48, 49], its structure was confirmed only after 30 years [50]. Pann arin (19)
was initially isolated from the lichens of Pannaria genus: P. lanuginosa, P. fulvescens, and
P. lurida [51], P. pityrea, P. rubiginosa, and later from Lecanora hercynica, Bombyliospora
HALOGENATED PHENOL COMPOUNDS IN LICHENS AND FUNGI
japonica [9, 25, 52] and Eriodeerma chilense [53].
The structure of pannarin (19) was additionally
investigated by other authors [54, 55]. Three depsidones compounds: nidulin (20), nornidulin (21)
and dechloronornidulin (22) were initially discovered in fungi belonging to the Aspergillus genus: A. nidulans [56–58], A. ustus [59, 60], A.
unguis [61], while nidulin (20) was also discovered in Emericella unguis lichen [62, 63].
Vicanicin (23), which was initially discovered in Telischistes flavicans lichen [64, 65], was
later isolated from other species: Caloplaca sp.
[66, 67], Psoroma sphinctrinum [68], P. allorhizum [69] and Erioderma chilense [70]. Norvicanicin (24) [68, 71] and isovicanicin (25) [71]
are emtabolytes in Psoroma athrophyllum [68,
559
69, 71], while O-methylvicanicin (26) is a metabolite of Erioderma sp. [71, 72]. The Caloplaca
sp. [66, 67] lichen generates caloploicin (27); its
structure was confirmed by synthesis [73].
The Aspergillus unguis fungus (hyphomycete group Hyphomycetales) relates to the most
widespread imperfect fungi. Aspergil colonies
forming mold coatings of bluish-green colour,
or other colours more rarely, are observed on
the products of plant origin. A number of toxins, such as haiderin (28), roubinin (29), shirin (30) and n asrin (31), are generated by Aspergillus unguis fungus [74]. Structurally similar 2-chlorounguinol (32), as well as emeguicins A–C (33)–(35) were detected in Emericella
unguis lichen [62, 63]. The metabolite 1-chlo-
560
VALERY M. DEMBITSKY a nd GENRICH A. TOLSTIKOV
ropann arin (36) known also as argopsin, with
its structure established by chlorination of pannarin (19) [75], was isolated from Agropsis megalospora lichen. This metabolite was also discovered in such lichens as Agropsis friesiana (otherwise called Agropsis megalospora) [55], Erioderma chilense [53, 70], E. phaeorhizym and E.
tomentosum [71]. Eriodermin (37) was discovered in Erioderma phyyscioides [76] and E. phaeorhizum [71]. The E. chilense lichen generates
norpannarin (38) and norargopsin (39) [53].
Physcosporin (40), a new chlorine-containing depsidones, was isolated from water-methanol extracts of Pseudocyphellaris physciospora lichen growing in Can ada [77] and in Europe [78]. It was also discovered among metab-
olites of P. granulata [78, 79] and P. flaveolata [79]. Physcosporin (40), hypophyscosporin
(41) and 3-O-methyl-physcosporin (42) are
present among the extractives from Erioderma phaeorhizum lichen [71]. The Australian
lichen Lecidea sp. generates lecideoidin (43)
and its dechlorin ated an alogue 3'-dechlorolecideoidin (44) [22]. Depsidones, namely, dechlorolecideoidins (45) and (46), along with scencidin (47) and compound (48), were discovered in Buellia canescens [80, 81]. 3-O-demethylscencidin (48) and O-methyldi ploicin (49)
were isolated from Australian lichen Di ploicia canescens [72].
Metabolite allorhizin (50) was found in Psoroma allorhizum lichen from New Zealand [69];
HALOGENATED PHENOL COMPOUNDS IN LICHENS AND FUNGI
four depsidones, i. e., phyllopsorin (51) and chlorophyllopsorins (52)–(54), are vital products of
the Australian lichen Phyllopsora coralline [82].
The Lecanora gangaleoides lichen synthesizes
leonidin (55) [33], while Fulgensia sp. generates
metabolite fulgidin (56) [83, 84].
The Chaetomium mollicellum fungus, which
belongs to the Chaetomiaceae family, is a typical
saprophyte inhabiting plant residues and taking active part in their decomposition. Chlorine-containing depsidones called mollicellins
D (57), E (58) and F (59) are synthesized by
Chaetomium mollicellum fungus [85].
Two metabolites, buellolide (60) and canescolide (61), which are lactones, are considered as
depsidones derivatives which can be formed
during their catabolism. These anomalous components are discovered in the Australian lichen Buellia canescens [80].
561
FUNGI PHENOL METABOLITES
About 800 different metabolites were discovered in fungi; however, only a small part
of them contained halogen atom. As a rule, it
was chlorine. The majority of chlorine-containing metabolites of parasitic fungi are toxic not
only for plants but also for animals and for
people.
A series of metabolites ilicolins A (62), C
(63), D (64), F (65) and E (66) are generated by
parasitic fungi Ascochyta viciae [86–88], Fusarium sp. [89] and Cylindrocladium ilicicola [90–
92]. For instance, fungi of the genus Ascochyta
cause extremely dangerous disease in above
ground organs of plants: leaves, stems and seeds.
The developing yellowish-brown spores strike
mainly legumes, in particular pea. On the contrary, fungi of the genus Fusarium strike rhizome of many plants, in particular cotton plant.
Fungi of the genus Cylindrocladium strike crucifers [93].
Another parasitic fungus species, Nectria
coccinea, which causes root rot and stem affection in different plants, generates chloronectrine (67) [94], while Ascochyta viciae fungus
generates compound (68) [95].
Pathogenous fungus Colletotrichum nicotianae
which affects tobacco plant generates such chlorine-containing metabolites as colletochlorines
562
VALERY M. DEMBITSKY a nd GENRICH A. TOLSTIKOV
D (69), B (70), A (71) and C (72) [96–98]. Ascofuranone (73) and ascofuranol (74) were discovered in Ascochyta viciae [99].
Ascochlorin (64) was discovered in Acremonium luzulae fungus [100]. Fungi Strobiluris tenacellus and Mycena sp. growing on rotten stubs
of conifers and deciduous trees generate one
and the same metabolite strobilurin (75) [101].
The history of strobilurin discovery is very
instructive. More than 20 years ago, strobilurins A and B, powerful fungicide compounds,
were isolated from mycelium of Strobiluris
mucida Basidiomycete. This stimulated investigations of secondary metabolites and various
fungi, including those parasitizing on trees.
Among them, chlorine-containing metabolites
were also discovered. At present, synthetic an-
alogues of strobilurins are developed and manufactured on industrial scale as the protective
means for agricultural plants.
Two chlorine-containing derivatives of
naphthalic acid (76) and (77) were found in
parasitic fungus Verticillium lamellicola which
HALOGENATED PHENOL COMPOUNDS IN LICHENS AND FUNGI
uses many plants and even fungi as substrates
[102]. Metabolite (72) was found in extracts of
Scolecobaasidiella avellanea fungus [103].
A series of new antibiotics (79)–(84) was
isolated from some cultivated fungi species.
Chlorine-containing antibiotic A30641 with unusual structure, which is also called aspirochlorin (79), is generated by several fungi species
belonging to the genus Aspergillus: A. tamarii
[104], A. flavus [105] and A. oryzae [106]. The
structure of aspirochlorin (79) was established
by means of X-ray structural an alysis [107];
synthesis of the antibiotic was carried out in
full [108]. Aspirochlorin (79) exhibited high antibacterial activity against pathogenous fungus
563
Candida albicans. It inhibits selectively the synthesis of some proteins, in particular the synthesis of RNA; however, the mechanism of
its action is not quite clear yet.
Antibiotics (80)–(84), possessing the structure
of the esters of 2-oxa-4-methoxy-5-chloro-6methyl benzoic acid with sesquiterpenic alcohols of the new structural type, are generated
by Armillaria mellea fungus which is called honey
mushroom. The first compound identified among
the indicated antibiotics was armillaridin (80)
[110]. It was followed by isolation of melleolide
D (81) [11, 112], melledonales B (82), C (83)
[113], then armillaricin (84) [114]. All these compounds exhibit antibacterial activity.
564
VALERY M. DEMBITSKY a nd GENRICH A. TOLSTIKOV
An interesting group of fungous metabolites is united by the presence of 3-oxabicyclo[4,4,0]deca-4,6-dien-8-one or 3-oxabicyclo[4,4,0]deca-1,4,6-trien-8-one fragments. For instance, soil fungus Emericella falconensis collected in Venezuela generates metabolites: falconensins A (85), C (86), B (87), D (88) [115],
and falconensin H (89) [116]. All of them are
esters of 2-methoxy-3,5-dichloro-4-oxy-6-methyl benzoic acid.
Metabolites of Penicillium and Chaetomium fungi are characterized by the presence of
trienic bicyclic fragment. Sclerotiorin (90) was
isolated from Penicillium sclerotiorum fungus
[117, 118]; its 7-epimer (91) and rubrotiorin
(92) were isolated from P. nirayamae [119–123].
The Chaetomium globossum fungi generate azaphilones A–D (93)–(96) [124]. Isochromophilones
(97)–(100) were isolated from cultural liquid
of Penicillium sp. fungus; it inhibits the growth
of HIV dr-120-CD4 cells [125].
REFERENCES
1 V. V. Zakharychev, L. V. Kovalenko, Uspekhi khimii,
67 (1998) 595.
2 H. Sauter, W. Steglich, T. Anke, Angew. Chem. Int.
Ed. Engl., 38 (1999) 1329.
3 S. Hunek and I. Yoshimura, Identification of Lichen
Substances, Springer-Verlag, Berlin – Heidelberg,
1996.
4 W. B. Turner, Fungal Metabolites, Acad. Press, New
York, 1971.
5 W. B. Turner and D. C. Aldridge, Fungal Metabolites, 2nd Edition, Acad. Press, New York, 1983.
6 M. Galun, CRC Handbook of Lichenology, Vol. I–III,
CRC Press, Boca Raton, Florida, 1988.
7 V. M. Dembitsky, T. Rezanka, I. A. Bychek and
M. V. Shustov, Phytochemistry, 31 (1992) 841.
8 V. M. Dembitsky, T. Rezanka and I. A. Bychek, Ibid.,
31 (1992) 1617.
9 V. M. Dembitsky, T. Rezanka and I. A. Bychek, Ibid.,
31 (1992) 851.
10 V. M. Dembitsky, I. A. Bychek and A. G. Kashin,
J. Hattori Botan. Lab., 71 (1992) 255.
11 T. Rezanka and V. M. Dembitsky, Phytochemistry,
50 (1999) 97.
12 T. Rezanka and V. M. Dembitsky, Ibid., 51 (1999) 963.
13 V. M. Dembitsky and M. Srebnik, Prog. Li pid Res.,
42 (2002) in press.
14 V. M. Dembitsky, I. A. Bychek and O. A. Rozentsvet,
Phytochemistry, 34 (1993) 1535.
15 V. M. Dembitsky, Prog. Li pid Res., 31 (1992) 373.
16 V. M. Dembitsky, Ibid., 35 (1996) 1.
17 A. S. Pfau, Helv. Chim. Acta, 17 (1934) 1319.
18 C. F. Culberton, Phytochemistry, 2 (1963) 335.
19 R. Ter-Heide, N. Provatoroff, P. C. Traas et al.,
J. Agric. Food Chem., 23 (1975) 950.
20 G. Koller and K. Popl, Monatsh., 64 (1934) 106.
21 G. Koller and K. Popl, Ibid., 64 (1934) 126.
22 C. F. Culberton, Chemical and Biological Guide to
Lichen Products, Chapel Hill, NC, University of
North Carolin a Press, 1969.
23 Y. Asahin a and F. Fuzikawa, Ach. Chem. Ber.,
68 (1935) 634.
24 S. Huneck and G. Follman, Z. Naturfosch.,
20B (1965) 1138.
25 Y. Asahina and F. Fuzikawa, Chem. Ber., 68 (1935) 2026.
26 C. F. Culberton, J. Pharm. Sci., 54 (1965) 1815.
27 P. Lee and K. Chantrapromma, Warasan Songkhla
Nakkaharin (India), 5 (1983) 149.
28 J. A. Elix and U. Engkanin an, Aust. J. Chem.,
29 (1976) 2701.
29 J. A. Elix, V. K. Jayanthi and C. C. Leznoff, Ibid.,
34 (1981) 1757.
30 S. Caccamese, R. M. Toscano, F. Bellesia and A. Pinetti, J. Nat. Prod., 48 (1985) 157.
31 T. J. Nolan, Sci. Proc., Roy. Dublin Soc., 21 (1936) 67.
32 P. A. Spillane, J. Keane and T. J. Nolan, Ibid.,
21 (1936) 333.
33 C. F. Culberton, Phytochemistry, 4 (1965) 951.
34 S. Huneck and J. Santesson, Z. Naturforsch.,
24B (1969) 756.
35 D. O. Chester, J. A. Elix and A. J. Jones, Aust. J. Chem.,
32 (1979) 1857.
36 P. Sevilla-Santos and L. M. Joson, J. Sci. (Phili ppine), 98 (1969) 1.
37 J. A. Elix, Aust. J. Chem., 28 (1975) 849.
38 S. Huneck, C. Dierassi, D. Becher et al., Tetrahedron, 24 (1968) 2707.
39 T. Hirayama, F. Fujikawa, I. Yosioka and I. Kitagawa, Chem. Pharm. Bull. (Japan), 24 (1976) 2340.
40 J. A. Elix, K. L. Gaul and P. W. James, Aust. J. Chem.,
38 (1985) 1735.
41 N. Hveding-Bergseth, T. Bruun and H. Kjosen, Phytochemistry, 22 (1983) 1826.
42 J. A. Elix and V. K. Jayanthi, Aust. J. Chem.,
40 (1987) 1851.
43 F. David, J. A. Elix and M. W. B. Samsudin, Ibid.,
43 (1990) 1297.
44 J. A. Elix, G. A. Jenkins and H. T. Lumbsch, Mycotaxon, 35 (1989) 169.
45 S. Huneck and J. Santensson, Z. Naturforsch.,
24B (1969) 750.
46 G. Bendz, J. Santesson and C. A. Wachtmeister, Acta
Chim. Scand., 19 (1965) 1185.
47 G. Bendz, J. Santesson and C. A. Wachtmeister, Ibid.,
19 (1965) 1188.
48 S. Huneck and G. Follman, Z. Naturforsch.,
20B (1965) 611.
49 S. Huneck, Chem. Ber., 99 (1966) 1106.
50 W. S. G. Maas and A. W. Hanson, Z. Naturforsch.,
41B (1986) 1589.
51 J. A. Elix, J. H. Mahadevan and J. H. Wardlaw, Aust.
J. Chem., 40 (1987) 1581.
52 J. A. Elix, D. O. Chester, K. L. Gaul et al., Ibid.,
42 (1989) 1191.
53 J. A. Elix, A. L. Wilkins and J. H. Wardlaw, Ibid.,
40 (1987) 2023.
54 S. Huneck, G. Hofle and C. F. Culberon, Phytochemistry, 16 (1977) 995.
55 S. Huneck, G. Sundholm and G. Follman, Ibid.,
19 (1980) 645.
HALOGENATED PHENOL COMPOUNDS IN LICHENS AND FUNGI
56 J. A. Elix, J. E. Evans and T. H. Nash III, Aust. J.
Chem., 41 (1988) 1789.
57 J. Nielsen, P. H. Nielsen and J. C. Frisvad, Phytochemistry 50 (1999) 263.
58 W. Zopf, Ann., 336 (1904) 46.
59 T. J. Nolan, Chem. Ind., (1934) 512.
60 T. J. Nolan, J. Algar, E. P. McCann et al., Sci. Proc.,
Roy Dublin Soc., 24 (1948) 319.
61 J. Hardiman, J. Keane and T. J. Nolan, Ibid.,
21 (1935) 141.
62 V. E. Davidson, J. Keane and T. J. Nolan, Ibid.,
23 (1943) 143.
63 M. V. Sargent, P. Vogel and J. A. Elix, J. Chem. Soc.,
Perkin Trans I, (1975) 1986.
64 I. Yosioka, J. Pharm. Soc. Japan, 61 (1941) 332.
65 S. Huneck, Z. Naturforsch., 21B (1966) 80.
66 J. A. Elix and U. A. Jenie, Aust. J. Chem., 39 (1986) 719.
67 D. A. Jackman, M. V. Sargent and J. A. Elix, J. Chem.
Soc., Perkin Trans I, (1975) 1979.
68 S. Huneck
and
I. M. Lams,
Phytochemistry,
14 (1975) 1625.
69 W. E. Doering, R. J. Dubos, D. S. Noyce and R. Dreyfus, J. Amer. Chem. Soc., 68 (1946) 725.
70 F. M. Dean, J. C. Roberts and A. Robertson, J. Chem.
Soc., (1954) 1432.
71 F. M. Dean, A. D. T. Erni and A. Robertson, Ibid.,
(1956) 3545.
72 W. F. Beach and J. H. Richards, J. Org. Chem.,
28 (1963) 2746.
73 J. M. Kurung, Science, 102 (1945) 11.
74 A. Kamal, Y. Haider, Y. A. Khan et al., Pakistan J.
Sci. Ind. Res., 13 (1970) 244.
75 N. Kawahara, S. Nakajima, Y. Satoh et al., Chem.
Pharm. Bull. (Japan), 36 (1988) 1970.
76 N. Kawahara, K. Nozawa, S. Nakajima et al., J. Chem.
Soc., Perkin Trans I, (1988) 2611.
77 S. Neelakantan, T. R. Seshadri and S. S. Subramanian, Tetrahedron Lett., 9 (1959) 1.
78 S. Neelakantan, T. R. Seshadri and S. S. Subramanian, Tetrahedron, 18 (1962) 597.
79 I. Yosioka, K. Hino, M. Fujio and I. Kitagawa, Chem.
Pharm. Bull. (Japan), 19 (1971) 1070.
80 I. Yosioka, K. Hino, M. Fujio and I. Kitagawa, Ibid.,
21 (1973) 1547.
81 M. V. Sargent, P. Vogel, J. A. Elix and B. A. Ferguson, Aust. J. Chem., 29 (1976) 2263.
82 J. A. Elix, L. Lajide and D. J. Galloway, Ibid.,
35 (1982) 2325.
83 W. Quilhot, B. Didyk, V. Gambaro and J. A. Garbarino, J. Nat. Prod., 46 (1983) 942.
84 A. L. B. Hamat, L. B. Din, M. W. B. Samsudin and
J. A. Elix, Aust. J. Chem., 46 (1993) 153.
85 J. A. Elix, G. A. Jenkins and D. A. Ven ables, Ibid.,
46 (1993) 197.
86 M. V. Sargent and P. Vogel, Ibid., 29 (1976) 907.
87 L. Kamal, Y. Haider, A. A. Qureshi and Y. A. Khan,
Pakistan J. Sci. Ind. Res., 13 (1970) 364.
88 B. Bodo and D. Molho, C.R. Acad. Sci. Paris, Ser. 2,
278 (1974) 625.
89 J. D. Connoly, A. A. Freer, K. Kalb and S. Huneck,
Phytochemistry, 23 (1984) 857.
90 W. S. G. Maas, A. G. McInnes, D. G. Smith and A. Taylor, Can J. Chem., 55 (1977) 2839.
91 B. Renner, A. Hensen and E. Gerstner, Z. Naturforsch., 33C (1978) 826.
565
92 E. M. Goh and A. L. Wilkins, J. Chem. Soc., Perkin
Trans I, (1979) 1656.
93 T. Sala, M. V. Sargent and J. A. Elix, Ibid., (1981) 849.
94 M. M. Mahandru and A. Tajbakhsh, Ibid., (1983) 413.
95 J. A. Elix, D. A. Ven ables and L. Brako, Aust. J. Chem.,
43 (1990) 1953.
96 J. A. Elix, A. A. Whitton and M. V. Sargent, Prog.
Chem. Org. Nat. Prod., 45 (1984) 103.
97 M. M. Mahandru and O. L. Gilbert, Bryologist,
82 (1979) 302.
98 G. Buchi and P. G. Williard, Heterocycles, 11 (1978) 437.
99 G. Tamura, K. Ando, S. Suzuki et al., J. Antibiot.,
21 (1968) 539.
100 Y. Nawata, K. Ando, G. Tamura et al., Ibid.,
22 (1969) 511.
101 Y. Nawata and Y. Iitaka, Bull. Chem. Soc. Japan,
44 (1971) 539.
102 G. A. Ellestad, R. H. Evans and M. P. Kunstmann,
Tetrahedron, 25 (1972) 1323.
103 H. Min ato, T. Katayama and S. Hayakawa, J. Antibiot., 25 (1972) 315.
104 A. Kato, K. Ando, G. Tamura and K. Arima, Ibid.,
23 (1970) 168.
105 S. Hayakawa, H. Min ato and K. Katagiri, Ibid.,
24 (1971) 6
106 Mir rasteniy: Griby, vol. 2, in A. L. Takhtazhdan
(Ed.), Prosveshcheniye, Moscow, 1991.
107 D. C. Aldridge, A. Borrow, R. G. Foster et al., J.
Chem. Soc., Perkin Trans I, (1972) 2136.
108 H. Sasaki, T. Hosokawa, Y. Nawata and K. Ando,
Agric. Biol. Chem., 38 (1974) 1463.
109 Y. Kosuge, A. Suzuki, S. Hirata and S. Tamura,
Ibid., 37 (1973) 455.
110 Y. Kosuge,
A. Suzuki
and S. Tamura, Ibid.,
38 (1974) 1265.
111 Y. Kosuge,
A. Suzuki and S. Tamura, Ibid.,
38 (1974) 1553.
112 H. Sasaki, T. Hosokawa, M. Sawada and K. Ando,
J. Antibiot., 26 (1973) 676.
113 N. Cagnoli-Bellavita, P. Ceccherelli, R. Fringuelli and
M. Ribaldi, Phytochemistry, 14 (1975) 807.
114 G. Schramm, W. Steglich and T. Anke, Chem. Ber.,
111 (1978) 2779.
115 N. J. McCorkindale, S. A. Hutchinson, A. C. McRitchie
and G. R. Sood, Tetrahedron, 39 (1983) 2283.
116 D. H. Berg, R. P. Massing, M. M. Hoehn et al.,
J. Antibiot., 29 (1976) 394.
117 T. P. Curtin and J. Reilly, Biochem. J., 34 (1940) 1419.
118 J. H. Birkinshaw, Ibid., 52 (1952) 283.
119 S. Udagawa, Chem. Pharm. Bull. (Japan),
11 (1963) 366.
120 E. M. Gregory and W. B. Turner, Chem. Ind.,
(1963) 1625.
121 G. A. Ellestad and W. B. Whalley, J. Chem. Soc.,
(1959) 3004.
122 R. W. Gray and W. B. Whalley, J. Chem. Soc. C,
(1971) 3575.
123 R. W. Gray and W. B. Whalley, J. Chem. Soc., Chem.
Commun., (1970) 762.
124 M. Takashi, K. Koyama and S. Natori, Chem. Pharm.
Bull. (Japan), 38 (1990) 625.
125 S. Omura, H. Tan aka, K. Matsuzaki et al., J. Antibiot., 46 (1993) 1908.